Congestive heart failure (CHF) is a complex syndrome characterized by multiple symptoms including fluid retention and shortness of breath (dyspnea). Although these symptoms are currently generally treated by oral loop diuretics, intravenous (IV) delivery of loop diuretics provides more rapid and complete relief, with many hospital visits primarily to obtain this benefit. The goal of this proposal is to develop a device that rapidly delivers loop diuretics into systemic circulation via deep lung inhalation, providing the benefits of IV loop diuretics to outpatients. Our company has developed an aerosol generation technology that enables rapid and reproducible delivery of many FDA-approved drugs to the systemic circulation using a compact, disposable inhaler. In this Phase I grant application we will prove the feasibility of using this technology to deliver one loop diuretic. In a subsequent Phase II grant application, we will optimize the inhaler for use by patients with CHF and complete the inhalation toxicology studies necessary for filing an Investigational New Drug Application (IND) with the FDA. Clinical development of the new treatment of dyspnea in patients with CHF would then be funded by outside investors or through a partnership with a major pharmaceutical company. Development and eventual FDA-approval of this product will enable patients with CHF to treat their dyspnea more effectively in out-of-hospital setting, thus decreasing burden on the health care system and improving quality of life for patients with CHF.